Translational evaluation of the Hypothalamus-Pituitary-Adrenal axis and the early life stress-induced allostatic load roles on neuroprogression and vulnerability to psychopathologies

• Grant number: 15/18773-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: March 01, 2016
• End date: September 30, 2019
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Norberto Garcia Cairasco
• Grantee: Eduardo Henrique de Lima Umeoka
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 14/12559-5 - Posttraumatic stress disorder and neuroprogression: new approaches to understand the effects of violence on mental functioning, AP.TEM
• Associated scholarship(s): 16/21369-0 - Early life adversity and fear memories: trans-generational effects and targeting the HPA axis with potentially therapeutic compounds, BE.EP.PD

Abstract

Stress, in Medicine, can be defined as the state of an organism aiming to reestablish the dynamic equilibrium, which was threatened or disrupted by physic or psychological factors. Depression affects millions of people, causing huge impact on quality of life of patients. Projections estimate that until 2020 there will be 121 millions of people with depression in the world. Stress seems to be the main environmental factor that predisposes an individual to depression. In around 60% of the cases, depressive episodes are preceded by stressful factor, especially psychosocial factors. Early-life adversities, such as abuse, neglect, parental lost are associated with higher risk of depression onset in human, or depressive-like behaviors in laboratory animals. More than elevated risk for depression, early-life stress can alter the clinic curse of the disease and influence the treatment prognostic. By means of experimental protocol to induce early-life stress, which lead the animals to display depressive-like behavior when adults, we will evaluate: a) biological markers associated wit the HPA axis activity, the main effector of the stress response highly associated with psychiatry diseases; b) effects of early-life stress over depressive-like behavior and cognitive performance; c) HPA axis responsiveness under pharmacological stimulation with corticosterone receptors agonists and antagonists, in a protocol similar to the protocol used in patients from "Hospital Dia" at the Riberião Preto School of Medicine; d) epigenetic alterations in response to the early-life stress protocol; e) the influence of gender and its correlation with the other parameters; f) the correlations between endocrine, cognitive and molecular parameters with the phenotypes assessed by behavior analyses and gender. This way we aim to obtain a translational and panoramic overview of the early-life stress effects on vulnerability to depression. Using an integrative approach (behavior, cognitive and molecular) we aim to suggest possible biomarkers for depression aiming to help diagnosis and treatment of depression

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

UMEOKA, EDUARDO H.; EIRAS, MATHEUS C.; VIANA, IARA G.; GIORGI, VANESSA S.; BUENO, ALINE; DAMASCENO, DEBORA C.; GARCIA-CAIRASCO, NORBERTO; NAVARRO, PAULA A.. Maternal reproductive performance and fetal development of the Wistar Audiogenic Rat (WAR) strain. SYSTEMS BIOLOGY IN REPRODUCTIVE MEDICINE, v. 65, n. 1, p. 87-94, JAN 2 2019. (15/18773-1)

GODOY, LIVEA DORNELA; ROSSIGNOLI, MATHEUS TEIXEIRA; DELFINO-PEREIRA, POLIANNA; GARCIA-CAIRASCO, NORBERTO; DE LIMA UMEOKA, EDUARDO HENRIQUE. A Comprehensive Overview on Stress Neurobiology: Basic Concepts and Clinical Implications. FRONTIERS IN BEHAVIORAL NEUROSCIENCE, v. 12, JUL 3 2018. (17/11339-0, 14/17959-1, 16/21369-0, 15/18773-1)

GODOY, LIVEA DORNELA; UMEOKA, EDUARDO H. L.; RIBEIRO, DEIDIANE ELISA; SANTOS, VICTOR RODRIGUES; ANTUNES-RODRIGUES, JOSE; LOURENCO JOCA, SAMIA REGIANE; GARCIA-CAIRASCO, NORBERTO. Multimodal early-life stress induces biological changes associated to psychopathologies. Hormones and Behavior, v. 100, p. 69-80, APR 2018. (13/01737-7, 17/11339-0, 15/18773-1, 14/17959-1)

BARROCA, NAYARA COBRA BARREIRO; DELLA SANTA, GIOVANNA; SUCHECKI, DEBORAH; GARCIA-CAIRASCO, NORBERTO; UMEOKA, EDUARDO HENRIQUE DE LIMA. Challenges in the use of animal models and perspectives for a translational view of stress and psychopathologies. NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS, v. 140, p. 19-pg., 2022-07-20. (15/18773-1, 17/10484-6)

BUURSTEDE, JACOBUS C.; UMEOKA, EDUARDO H. L.; DA SILVA, MARCIA SANTOS; KRUGERS, HARM J.; JOELS, MARIAN; MEIJER, ONNO C.. Application of a pharmacological transcriptome filter identifies a shortlist of mouse glucocorticoid receptor target genes associated with memory consolidation. Neuropharmacology, v. 216, p. 11-pg., 2022-07-12. (16/21369-0, 15/18773-1)